Cells communicate by changing their environment

Researchers at IBEC and MIT have shown that cells could use their environment to mechanically communicate with each other within tissues. It’s a bit like when an army cadet pulls some rope netting taut so that his friend can safely ascend.

To nourish our organs and tissues, cells need to constantly detect and respond to the mechanical stimuli from their environment. Generally, cells that make up the tissues in our bodies are immersed in an extracellular matrix (ECM), ​​a biopolymer made of proteins and glycoproteins such as collagen or fibrin. This ECM provides the cells with a way to interact with other cells, obtain nutrients, eliminate waste and ultimately form an integral and functional tissue.

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Cell contraction causing stiffness in an extracellular matrix. In blue, the cell; in green, the collagen matrix.

Whether the cells are moving, dividing or differentiating, the ECM plays a major role in cellular function, so it’s vital to have a good understanding of cell-matrix interactions. However, it remains largely unknown how cells, in turn, affect the mechanics of this surrounding matrix. Not only that, but changes in the ECM triggered by the cells can also propagate, affecting neighbouring cells.

During his research stay in Roger Kamm’s mechanobiology lab at MIT in 2015-2017, IBEC postdoc Andrea Malandrino was involved in the development of a method, which they’re calling nonlinear stress inference microscopy (NSIM), that reveals in 3D the mechanical stresses that the cells cause to the ECM based on locally measuring its rigidity.

“We found that cells contracting is a cause of local hardening in the ECM,” says Andrea. “We saw, also, that this transmits mechanical changes like stiffening on a larger scale, spreading beyond the original cell. This suggests a concrete mechanism through which cells can control their microenvironment and mechanically communicate with each other, which could explain phenomena such as durotaxis, a type of cell migration.”

Further knowledge about this mechanism could lead to a better understanding of phenomena such as the stiffening of tissues that occurs in tumours or fibrotic diseases.

Yu Long Han, Pierre Ronceray, Guoqiang Xu, Andrea Malandrino, Roger Kamm, Martin Lenz, Chase P. Broedersz and Ming Guo (2018). Cell contraction induces long-ranged stress stiffening in the extracellular matrix. PNAS, epub ahead of print.